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ID: ALA3797059
Journal: Bioorg Med Chem Lett
Title: Design, synthesis and biological evaluation of pyrazolylaminoquinazoline derivatives as highly potent pan-fibroblast growth factor receptor inhibitors.
Authors: Fan J, Dai Y, Shao J, Peng X, Wang C, Cao S, Zhao B, Ai J, Geng M, Duan W.
Abstract: Fibroblast growth factor receptors (FGFRs) are important oncology targets due to the dysregulation of this signaling pathway in a wide variety of human cancers. We identified a series of pyrazolylaminoquinazoline derivatives as potent FGFR inhibitors with low nanomolar potency. The representative compound 29 strongly inhibited FGFR1-3 kinase activity and suppressed FGFR signaling transduction in FGFR-addicted cancer cells; FGFRs-driven cell proliferation was also strongly inhibited regardless of mechanistic complexity implicated in FGFR activation, which further confirmed that 29 was a potent pan-FGFR inhibitor. The flexibility of our structure offered the potential to preserve good affinity for mutant FGFR, which is important for developing TKIs with long-term efficacy.
CiteXplore: 27117427